| Background Hepatocellular carcinoma（HCC）is the leading cause of fatal tumors worldwide.Hepatocellular carcinoma（HCC）is one of the most common types of liver cancer..Difficulties in early diagnosis,few treatment options,and poor survival are major challenges for HCC patients.Due to the complexity and diversity of pathogenesis,clinical strategies for different types of HCC vary widely,seriously affecting the quality of life of patients.The etiology of the disease is not fully understood,and little progress has been made in identifying early risk biomarkers.Therefore,effective markers for early detection of Hepatitis B-associated HCC are lacking.liver,the body’s most important metabolic organ,the development or progression of hepatocellular carcinoma（HCC）is closely related to liver metabolism.Studies have shown significant changes in serum metabolite biomarkers in the early stages of HCC development.As a result,metabolic biomarkers for HCC diagnostic validation have received widespread attention,and high-throughput sequencing（HFSCS）techniques have rapidly developed in early cancer diagnosis,tumor typing,tumor progression,genomic molecular markers,drug screening targets,and molecular basis for guiding personalized medicine.Objective In this study,untargeted metabolomics and transcriptomics were used to analyze the differentially expressed genes and metabolites in HBV-related hepatocellular carcinoma and identify potential new diagnostic targets.Methods We applied HBV plasmid to transfect Huh7 hepatocellular carcinoma cells and used western blot to detect the relative expression of HBs Ag in the cells before and after transfection.Metabolomics samples were harvested,and liquid chromatography/mass spectrometry（LC/MS）analysis was applied to screen out differentially expressed metabolites.then KEGG pathway enrichment analysis was performed on the differentially expressed metabolites.Transcriptome samples were collected,differentially expressed genes were screened using whole-transcriptome analysis,and differentially expressed genes were analyzed using GO entries and KEGG pathway enrichment.Finally,we performed association analysis of metabolomics and transcriptomics esults based on statistical methods and metabolic pathways.Results HBs Ag was highly expressed in the experimental group after HBV transfection.LC/MS results showed that HBV transfection could lead to significant upregulation of 57 metabolites and significant downregulation of 33 metabolites.The differential metabolites were mainly enriched in the metabolic pathways of steroid hormone biosynthesis,purine metabolism,amino sugar and nucleoside sugar metabolism.RNA-seq results showed that that HBV transfection could lead to significant upregulation of 387 genes and significant downregulation of 44 genes.The differentially expressed genes were highly enriched in GO terms associated with extracellular matrix binding、collagen binding and fatty acid ligase activity.KEGG pathway enrichment results indicated that differentially expressed genes were highly concentrated in PI3 K Akt signaling pathway,cell adhesion molecules（CAMs）and c AMP signaling pathway.The results of multi omics association analysis showed that the differentially expressed genes and metabolites were co enriched in several metabolic pathway categories: amino acid metabolism,cofactors and vitamins,lipid metabolism,carbohydrate metabolism and exogenous compound metabolism.Based on the result analysis and literature collection,we identified the association of 18 genes and 15 metabolites and mapped the association network.Conclusion HBV infection abnormally regulates the differential expression of 18 genes and leads to the abnormal expression of liver metabolites.The 15 abnormally expressed metabolites identified in this study may provide a theoretical basis for new markers for the early diagnosis of HBV-related hepatocellular carcinoma. |
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